Ebolaviruses (EboV) are enveloped negative-sense RNA viruses that cause sporadic outbreaks of rapidly fatal zoonotic infection. EboV is transmitted by close contact and virus levels increase by 75-fold/day for several days after initial infection. The clinical symptoms are manifestations of the massive production of pro-inflammatory cytokines, including interferon-α and TNF-α in response to infection. The endothelial cell dysfunction associated with “cytokine storm” results in capillary leak, hypovolemic shock, disseminated intravascular coagulation and inadequate perfusion of major organs. In many outbreaks, the mortality rate from EboV infection exceeds 75% in 14 days. Current therapy is supportive; there is no effective anti-EboV vaccine or therapy. The unpredictable onset, ease of transmission, rapidity of progression, high mortality, and bio-terrorism potential have created a high level of public concern about EboV. Therefore, development of anti-EboV drugs is a high priority.
Recent studies have identified promising drug targets. Previously, it was found that stepwise proteolytic cleavage of EboV envelope glycoprotein GP by the lysosomal cysteine proteases cathepsin L (Cat L) and cathepsin B (Cat B) is required for infection; and therefore, inhibitors of Cat L and Cat B are potential anti-EboV drugs (see, for example, US Patent Application publication number 2009/0053263 to Cunningham, J. et al.).